Extraovarian Endometriosis Research Articles

P-743 Laparoscopic radical excision of deep endometriosis: A positive impact of fertility outcome

Abstract Study question Does laparoscopic radical excision of deep endometriosis (DE) and endometrioma enucleation impact fertility outcomes and recurrence rates when compared to partial excision group? Summary answer In stage IV endometriosis, laparoscopic radical surgery significantly reduced the recurrence rates.The laparoscopic radical excision group tended to have a higher rate of natural conception. What is known already Endometriosis-related symptoms can be significantly improved through surgery, leading to better pregnancy rates. However, the optimal surgical approach can vary due to the complexity of DE. As a result, the recurrence of postoperative symptoms and pregnancy rates can differ due to the lack of randomized trials comparing primary surgery with first-line IVF studies. Thus, the ESHRE stated that there was no evidence supporting surgical management of DE prior to ART to improve pregnancy rates. However, the higher probability of postoperative spontaneous conception in patients undergoing radical resection versus conservative treatment of DE has been reported. Study design, size, duration study design: Retrospective cohort study in a tertiary referral center. size: 77 patients diagnosed with moderate or severe endometriosis and DE. duration: between 2018 and 2020 Participants/materials, setting, methods 77 patients underwent laparoscopic surgery for dysmenorrhea or infertility. Group 1 (n = 22) underwent conservative treatment through partial excision of endometriosis, indicating incomplete resection. Group 2 (n = 55) underwent radical excision of endometriosis and restoration of pelvic anatomy, indicating complete resection. We compared the baseline characteristics, peri-operative data, and follow-up outcomes, aiming to investigate whether radical excision yields superior results in terms of recurrence rate, re-intervention, and pregnancy rate. Main results and the role of chance Main results: Group 2 showed significantly higher surgical complexity with higher revised American Fertility Society classification scores, a greater proportion of severe endometriosis, multiple sites with endometriotic lesions, and longer operation times. Both groups had comparable pregnancy, recurrence, and re-intervention outcomes during the follow-up period of 28.2±16.4 months. While Group 2 tended to have a higher pregnancy rate (84% versus 67%, p = 0.56) and higher live birth rates (80% versus 67%, p = 0.59) when compared with group 1. In the population with stage IV endometriosis, group 2 significantly reduced the recurrence rates (9% versus 50%, p = 0.04) when compared to group 1. Conclusions: The group that underwent laparoscopic endometrioma enucleation with radical excision of extra-ovarian endometriosis exhibited significantly higher surgical complexity. In the population with stage IV endometriosis, radical surgery significantly reduced the recurrence rates. Surgical excision of ovarian endometriosis and extra-ovarian disease is advisable to limit disease progression and ensure complete symptom resolution. Additionally, the laparoscopic radical excision group tended to have a higher rate of natural conception, indicating potential benefits for fertility in patients who have moderate and severe endometriosis with DE. Limitations, reasons for caution The main limitations were the small sample size and recall bias. But, additionally, the limited cases in the research group might have influenced the results and restricted the extrapolation of related conclusions. Further studies with larger sample sizes are needed in the future. Wider implications of the findings We believe that a standardized surgical technique outlining a step-by-step method to delineate all important structures and address altered planes as in endometriosis, with the aim of restoring normal pelvic anatomy, ensures the avoidance of high complication rates, leads to lower recurrence rates and positive impact on fertility outcomes. Trial registration number not applicable

Primary Retroperitoneal Carcinomas: New Insights into Pathogenesis and Clinical Management in Comparison with Ovarian Carcinomas and Carcinoma of Unknown Primary.

Primary retroperitoneal carcinomas are very rare tumors. Their pathogenesis remains unknown but may be associated with that of ovarian carcinomas, considering the similarity in morphology and gender preference. Although metaplasia of coelomic epithelium is the most widely accepted theory, the pathogenesis of retroperitoneal carcinomas may differ by histologic subtype, like ovarian carcinomas. Mucinous carcinoma, which develops in both women and men, may originate in both primordial germ cells and Walthard cell nests that may be derived from the fallopian tube. Serous carcinomas may be associated with endosalpingiosis, the presence of fallopian tube-like epithelium outside the fallopian tube, and a remnant Müllerian tract. Endometrioid and clear cell carcinomas appear to be associated with extraovarian endometriosis. Additionally, both carcinomas in the retroperitoneal lymph nodes may be metastatic diseases from endometrial and/or renal cell cancer that regress spontaneously (carcinoma of unknown primary). Retroperitoneal carcinomas are difficult to diagnose, as they have no characteristic symptoms and signs. Surgery is the cornerstone of treatment, but the necessity of chemotherapy may depend on histological subtype. Further studies are necessary, in particular studies on endosalpingiosis, as endosalpingiosis is a poorly understood condition, although it is associated with the development of both serous and mucinous carcinomas.

Superinfection of Rectovaginal Endometriosis: Case Report and Review of the Literature.

A peculiar complication of endometriosis is a superinfection. However, the superinfection of extra-ovarian endometriosis is anecdotal, and only a few cases have been described. We wanted to present the first cases of the superinfection of rectovaginal endometriosis and to perform a literature review of the superinfection of extra-ovarian endometriosis. We present a case of a 24-year-old woman who was referred to our Pelvic Floor Unit for rectal-perineal pain, dyspareunia, and recurrent episodes of dense purulent vaginal discharge for one year, in which the superinfection of rectovaginal endometriosis was diagnosed. Moreover, we performed a systematic search of the literature indexed on PubMed up to 31 January 2023. Laparoscopic drainage was successful in managing this condition. In the literature, clinical presentation and instrumental and microbiological findings are very heterogeneous. However, the gold standard of management is represented by surgical or percutaneous drainage. In the case of a pelvic abscess, the superinfection of endometriosis lesions should be suspected, and this can represent the onset symptom of endometriosis. Ultrasonography may show nodular or flat hypoechoic lesions with hyperechoic debris and peripheral positive color/power Doppler intensities. The goal of management is to drain the abscess, either percutaneously or via traditional surgery, followed by proper hormonal therapy to reduce recurrence.

Malignancies Associated with Extraovarian Endometriosis: A Literature Review

Endometriosis-associated ovarian malignancies have been well documented. Although these malignancies also occur as extraovarian lesions, little is known about them. Thus, this literature review aimed to further explore these rarely experienced tumors. A total of 257 published cases between April 1990 and April 2020 were found using PubMed, and 212 cases were included in the analysis considering Sampson’s criteria and the history of endometriosis. We classified these cases as follows: intestine, abdominal scar, vagina and vulva, peritoneum and deep endometriosis, urinary tract, uterine cervix, and others. Age of patients, history of endometriosis, types of past hormonal therapy, symptoms, histological types, and treatment were identified. The most common tumor site was the intestine. Endometrioid carcinoma was the dominant histological type. Contrary to the ovary, clear cell carcinoma was rare in extraovarian sites. On the other hand, clear cell carcinoma represented the largest number of abdominal scars. This difference may help us to understand the development of endometriosis-related malignancies. Hormonal treatment was mentioned in 67 cases and estrogen replacement therapy in 33 cases. Although risks of estrogen therapy are still controversial, the highly differentiated histological types and hormone-dependent characteristics of endometriosis-associated malignancy should be considered. Physicians should be careful about estrogen monotherapy after hysterectomy and long-term hormone replacement therapy in patients with a history of endometriosis.

Extrauterine Mesonephric-like Neoplasms: Expanding the Morphologic Spectrum.

Mesonephric-like adenocarcinomas (MLA) are rare neoplasms arising in the uterine corpus and ovary which have been added to the recent 2020 World Health Organization Classification of Female Genital Tumors. They have similar morphology and immunophenotype and exhibit molecular aberrations similar to cervical mesonephric adenocarcinomas. It is debated as to whether they are of mesonephric or Mullerian origin. We describe the clinical, pathologic, immunohistochemical, and molecular features of 5 cases of extrauterine mesonephric-like proliferations (4 ovary, 1 extraovarian), all with novel and hitherto unreported features. These include an origin of MLA in extraovarian endometriosis, an association of ovarian MLA with high-grade serous carcinoma, mixed germ cell tumor and mature teratoma, and a borderline ovarian endometrioid tumor exhibiting mesonephric differentiation. Four of the cases exhibited a KRAS variant and 3 also a PIK3CA variant. In reporting these cases, we expand on the published tumor types associated with MLA and report for the first time a borderline tumor exhibiting mesonephric differentiation. We show the value of molecular testing in helping to confirm a mesonephric-like lesion and in determining the relationship between the different neoplastic components. We provide further evidence for a Mullerian origin, rather than a true mesonephric origin, in some of these cases. We also speculate that in the 2 cases associated with germ cell neoplasms, the MLA arose out of the germ cell tumor.

Coexistence of endometriomas with extraovarian endometriosis and adhesions

ObjectiveThe aim of the study is to show the coexistence of the endometriomas with peritoneal and deep infiltrating endometriosis, as well as with the adhesions.Study designIt's a randomized retrospective study. Patients treated for endometrioma at Academic Hospital Cologne Weyertal from January 2014 to October 2019 were included. In total there were 1054 patients. 310 medical records were chosen at random without a special selection and the data were analysed. ResultsIn our study, endometriomas were alone, which means without extraovarian endometriosis and/or adhesions, in only 2.3% of the cases. In the total population, 80.6% (250) of the patients had peritoneal endometriosis, 43.2% (134) of the patients had deep infiltrating endometriosis and 38% (118) of the patients had peritoneal and deep infiltrating endometriosis. In our analysis we found that in unilateral endometriomas there is no relationship between endometrioma size and adnexal adhesions. The risk of Douglas obliteration increases with the size of the endometriomas in unilateral endometriomas. In bilateral endometriomas, the risk of a complex adhesions is independent of the size of the endometriomas and relevantly higher than in unilateral endometriomas (Douglas obliteration 31.5% vs 16%, bilateral adnexal adhesions 45.2% vs 21.1%). Unilateral adnexal adhesions occurred in bilateral endometriomas only in 13.7%. ConclusionEndometriomas are the relevant problem in gynaecological practice. It must be taken into account here that endometriomas usually occur with peritoneal endometriosis and that surgical therapy may be useful. However, adhesions and DIE are to be expected with surgical treatment, which could make the operation more difficult. Especially in large and bilateral endometriomas, a high coexistence with extraovarian endometriomas and adhesions is observed. Therefore, surgery should be performed by an experienced surgeon.

Whole-Exome Sequencing of Rare Site Endometriosis-Associated Cancer.

Malignant transformation of extraovarian endometriosis is rare, with the carcinogenesis mechanism unclear. To clarify the actionable variants of rare-site endometriosis-associated cancer (RSEAC), we performed whole-exome sequencing for the tumor, in two patients. The intestine was affected in both cases, although the histology was that of clear cell carcinoma and undifferentiated carcinoma, respectively. Therefore, the cases were referred to as endometriosis-associated intestinal tumors (EIATs). Actionable variants (all frameshift mutations) were identified in tumor suppressor genes ARID1A, PTEN, and p53; however, no oncogenic variants were identified. Both cases were microsatellite stable. The patient with undifferentiated carcinoma exhibited hypermutator and homologous recombination deficiency phenotypes. The dominant mutation signatures were signature 30 (small subset of breast cancers) and 19 (pilocytic astrocytoma) in patient 1, and signature 5 (small subset of breast cancers) and 3 (breast, ovarian, and pancreatic cancers) in patient 2. Immunohistochemistry revealed positive CD8 and PD-1 expression in both patients; patient 1 also showed positive PDL-1 expression. Our results suggest that RSEAC is associated with variants of tumor suppressor genes as epigenetic alterations. Mutation signature-based whole-exome sequencing could be useful to select an adjuvant chemotherapy regimen. High CD8 and PD-1 expression in RSEAC suggests that immune checkpoint inhibitors are useful for treatment.

Malignant extra-ovarian endometriosis: A case series of ten patients and review of the literature.

The malignant transformation of endometriosis within the ovary is a recognised condition. There is less literature surrounding the malignant transformation of extra-ovarian endometriosis (MEOE). We report our experience with MEOE in ten patients and present a review of the literature regarding this rare malignancy. For this retrospective case series, patients were identified from a practice-based database. Where required, operative notes and pathology reports were reviewed. Ten patients diagnosed with MEOE between 1991 and 2014 were identified. In each case, the tumour was localised to the pelvis and centred on the pouch of Douglas, broad ligament, obturator fossa, parametrium and rectovaginal septum. Tumour histology was endometrioid adenocarcinoma (six), clear cell carcinoma (two), and adenosarcoma (two). Five patients had a history of endometriosis and four had received oestrogen-only hormone replacement therapy after hysterectomy and bilateral salpingo-oophorectomy. Treatments included surgery (one), surgery and radiotherapy (one), surgery and chemotherapy (one), surgery, radiotherapy and chemotherapy (three), and radiotherapy and chemotherapy (four). Maintenance hormonal therapy was also used in three patients. Curative doses of radiotherapy 45Gy or more resulted in in-field control in five patients. Six patients had no evidence of disease at a mean follow up period of 15years (5.5-24years). Severe G3 long-term bladder morbidity occurred in three patients after radical surgery and radiotherapy. MEOE is a rare condition for which treatment needs to be individualised. Multicentre studies and registries will hopefully define optimal treatment.

Cancers associated with extraovarian endometriosis at less common/rare sites: A nationwide survey in Japan.

Endometriosis mostly affects the ovary but can also be present outside of the ovary including the pelvic peritoneum, intestine, urinary tract and lung. In case of ovarian endometriotic cyst, an increased risk of ovarian cancer, especially of clear cell and endometrioid histology, has been reported. However, because of the rarity, cancer occurrence from endometriosis at less common sites/rare sites is poorly understood. We conducted a nationwide survey on the less common/rare site endometriosis in 3539 authorized facilities in Japan. We requested to complete a case report form for each case, including information on the history of endometriosis, treatment for endometriosis, type of surgery, involved site(s) of cancer and endometriosis, histology of cancer, chemotherapy and outcome. Out of 1397 confirmed cases of less common/rare site endometriosis, 11 cases of rare site endometriosis-associated cancer (RSEAC) were reported: seven of them were associated with intestinal endometriosis, three were associated with urinary tract endometriosis and one was associated with umbilical endometriosis. Interestingly, the histology was endometrioid in seven (64%) cases, and serous, seromucinous borderline, clear cell and mucinous in one case each (10%), differing from the case of ovarian endometriosis-associated cancer, in which clear cell carcinoma are more common. Our nationwide survey on RSEAC has revealed that: (i) the incidence of malignant transformation may be lower than ovarian endometriosis, (ii) malignant transformation from endometriosis outside the abdominal cavity may be extremely rare and (iii) the histology of RSEAC is predominantly endometrioid type, suggesting an association of a hormonal effect.

Endometrioid adenocarcinoma of rectum, a rare site for extraovarian endometriosis associated cancer

Endometrioid adenocarcinoma of rectum, a rare site for extraovarian endometriosis associated cancer

Secreted frizzled-related protein 2 (SFRP2) expression promotes lesion proliferation via canonical WNT signaling and indicates lesion borders in extraovarian endometriosis.

What is the role of SFRP2 in endometriosis? SFRP2 acts as a canonical WNT/CTNNB1 signaling agonist in endometriosis, regulating endometriosis lesion growth and indicating endometriosis lesion borders together with CTNNB1 (also known as beta catenin). Endometriosis is a common, chronic disease that affects women of reproductive age, causing pain and infertility, and has significant economic impact on national health systems. Despite extensive research, the pathogenesis of endometriosis is poorly understood, and targeted medical treatments are lacking. WNT signaling is dysregulated in various human diseases, but its role in extraovarian endometriosis has not been fully elucidated. We evaluated the significance of WNT signaling, and especially secreted frizzled-related protein 2 (SFRP2), in extraovarian endometriosis, including peritoneal and deep lesions. The study design was based on a cohort of clinical samples collected by laparoscopy or curettage and questionnaire data from healthy controls and endometriosis patients. Global gene expression analysis in human endometrium (n = 104) and endometriosis (n = 177) specimens from 47 healthy controls and 103 endometriosis patients was followed by bioinformatics and supportive qPCR analyses. Immunohistochemistry, Western blotting, primary cell culture and siRNA knockdown approaches were used to validate the findings. Among the 220 WNT signaling and CTNNB1 target genes analysed, 184 genes showed differential expression in extraovarian endometriosis (P < 0.05) compared with endometrium tissue, including SFRP2 and CTNNB1. Menstrual cycle-dependent regulation of WNT genes observed in the endometrium was lost in endometriosis lesions, as shown by hierarchical clustering. Immunohistochemical analysis indicated that SFRP2 and CTNNB1 are novel endometriosis lesion border markers, complementing immunostaining for the known marker CD10 (also known as MME). SFRP2 and CTNNB1 localized similarly in both the epithelium and stroma of extraovarian endometriosis tissue, and interestingly, both also indicated an additional distant lesion border, suggesting that WNT signaling is altered in the endometriosis stroma beyond the primary border indicated by the known marker CD10. SFRP2 expression was positively associated with pain symptoms experienced by patients (P < 0.05), and functional loss of SFRP2 in extraovarian endometriosis primary cell cultures resulted in decreased cell proliferation (P < 0.05) associated with reduced CTNNB1 protein expression (P = 0.05). SFRP2 and CTNNB1 improved extraovarian endometriosis lesion border detection in a relatively small cohort (n = 20), although larger studies with different endometriosis subtypes in variable cycle phases and under hormonal medication are required. The highly expressed SFRP2 and CTNNB1 improve endometriosis lesion border detection, which can have clinical implications for better visualization of endometriosis lesions over CD10. Furthermore, SFRP2 acts as a canonical WNT/CTNNB1 signaling agonist in endometriosis and positively regulates endometriosis lesion growth, suggesting that the WNT pathway may be an important therapeutic target for endometriosis. This study was funded by the Academy of Finland and by Tekes: Finnish Funding Agency for Innovation. The authors have no conflict of interest to declare.

Endometrial Stromal Sarcoma Arising from Endometriosis

The malignant transformation of endometriosis is a very uncommon event but can occur in 0.7% to 1% of all cases. Any histological type of tumor found in the endometrium might also occur in endometriosis. Most malignant tumors that originate from endometriosis are endometrioid adenocarcinomas and also clear-cell type carcinomas. On the other hand, sarcomas, especially endometrial stromal sarcoma (ESS), are extremely unusual representing 12% of all cases. ESS is an uncommon neoplasm and accounts for 0.2% of the uterine malignances. Malignant tumors arising from endometriosis can derive from the uterine wall as well as from extra-uterine sites. The most frequent extrauterine location is the ovary (78.7%), followed by the pelvic peritoneum (5.7%), the rectovaginal septum (4.3%), the colon (4.3%) and the vagina (2%), representing the majority of extragonadal sites. ESSs arising from the extrauterine and extraovarian endometriosis sites in the absence of a primary uterine lesion are extremely rare and the treatment options are not clear. Surgical debulking seems to be the best treatment. Adjuvant therapy, such as radiation, hormonal therapy and chemotherapy are not yet proven to be effective. Molecular target therapy could be a future possibility of treatment. A systematic review of English Medical Literature about incidence, treatment and prognosis of extrauterine ESS arising from endometriosis foci was performed. The selected articles on which this review is based are the following: 9 literature reviews, 8 retrospective studies, 7 case series, 1 prospective trial and 11 case reports.

Ovarian endometriosis and vitamin D serum levels

Aim: The aim of this study was to assess the vitamin D serum level in women with ovarian endometriosis; specifically, a possible correlation between the dimensions of ovarian endometriomas and vitamin D serum levels was evaluated.Materials and methods: This was an observational study of childbearing-age women diagnosed with singleton ovarian endometrioma from January 2015 to December 2015. Women diagnosed with multiple ovarian endometriomas or extraovarian endometriosis were excluded.Results: Forty-nine women constituted the initial study cohort. In these women, the mean (±SD) 25-OH-D3 serum level was 22.0 (±8.9) ng/ml, and 42 of them (85.7%) were diagnosed with hypovitaminosis D. In the “hypovitaminosis D women”, the mean (± SD) diameter of ovarian endometriomas was 40.2 ± 22.6 mm, while in the “normal vitamin D serum level women” it was 26.7 ± 12.1 mm (p = 0.1). However, a significant linear correlation between 25-OH-D3 serum level and the diameter of ovarian endometriomas was found (r = −0.3, p = 0.03).Conclusion: We found a relatively high rate of women with ovarian endometriosis and hypovitaminosis D. Interestingly, a significant linear correlation between 25-OH-D3 serum levels and the diameter of ovarian endometrioma emerged.

The Impact of Endometriosis and Its Treatment on Ovarian Reserve.

Endometriosis is a chronic disease mostly affecting women at reproductive age. There is a clear association between endometriosis and infertility; however, exact mechanisms are unknown. Some evidence suggests an adverse effect on oocytes. Endometriosis and its surgical treatment can affect quantitative ovarian reserve as well. In the presence of endometriomas, serum level of anti-Müllerian hormone (AMH) seems a more reliable marker of ovarian reserve than antral follicle count. Women with endometrioma have decreased serum AMH levels as compared with healthy controls. This is further declined after surgical excision, and the decline seems permanent. Bipolar cauterization of the ovary seems to be playing a role on ovarian damage. Extraovarian endometriosis and its surgical treatment can also be associated with decreased ovarian reserve, but there is limited information. Patients with endometriosis should be informed about fertility preservation options, especially in the presence of bilateral endometriomas or prior to surgery.

Systematic evaluation of women with suspected endometriosis using a 5-domain sonographically based approach.

In recent years, knowledge has evolved regarding the role of transvaginal sonography in the assessment of the pouch of Douglas status and the preoperative prediction of extraovarian endometriosis in specific locations. Despite these advances in transvaginal sonography, the challenge of developing a comprehensive, cost-effective, and reproducible preoperative classification system for endometriosis remains. Critical to this classification system should be a sonographically based evaluation protocol that is systematic, evidence based, and reproducible with clearly defined end points. To date, no structured evaluation protocol exists for the assessment of the pelvis in women with suspected endometriosis. In this article, we propose a domain-based evaluation protocol for the assessment of women with suspected endometriosis using transvaginal sonography.

Susceptibility-weighted MRI of extra-ovarian endometriosis: preliminary results.

Extra-ovarian endometriosis (EOE) usually appears as solid masses mimicking neoplasms both clinically and radiologically. Detection of blood products within a lesion may be suggestive of its endometriotic nature. We present a descriptive study of MR imaging findings that include susceptibility-weighted imaging (SWI) for patients with EOE. Eight pathologically proven EOE (3 bowel, 2 bladder and 3 abdominal wall) were evaluated. Fat-saturated T1-weighted images (fsT1WI) and SWI were obtained using 1.5T MR imaging. Images were reviewed for the presence of signal voids on SWI and of high-intensity foci on fsT1WI. High-intensity foci reflecting subacute hemorrhage were detected in 4 of 8 lesions (50%) on fsT1WI, whereas signal voids reflecting acute to chronic hemorrhage were detected in all 8 lesions (100%) on SWI. SWI is a sensitive MRI technique which demonstrates hemorrhage of varying chronicity in patients with EOE and may improve future MRI characterization of EOE.

Deep Endometriosis: Less is Better

many surgeons are considering any opportunity for medical treatment as a possible alternative and effective solution (8). Why? In our opinion and looking at the literature, there are different points to be addressed to better understand if this is a final step or a transitory philosophy. An enormous effort is still in process to enhance the possibility of diagnosing in the best and most accurate way not only the presence but also the size, number and localization of DIE to better counsel patients and guide surgeons. This clinical change is apparently very useful for reducing the number of complications and to inform preoperatively and in details patients scheduled for surgery. A correct diagnosis is fundamental in defining the best treatment strategy for endometriosis. Therefore, noninvasive methods are required to obtain an accurate evaluation of the location and extent of endometriotic lesions, such as transvaginal ultrasound (TVUS) and magnetic resonance imaging (MRI). The detection rate of imaging procedures is linked to the experience of the operator. The first-line modality is TVUS, which is deemed to be accurate in detecting both ovarian and extraovarian endometriosis. MRI has shown comparable results with those of TVUS in the assessment of deep endometriosis (9-11). Different authors describes that the dynamic view of the pelvis obtained by TVUS performed by skill operator, allows to give to the surgeons all the informations needed preoperatively by the surgeon. A more strict collaboration among surgeons and diagnosticians is suggested to match the preoperative assessment their experiences. Endometriosis, especially in its more severe expression, needs to be treated by very skilled surgeons able to perform difficult procedures accurately. Surgical treatment must be performed by surgeons dedicated to endometriosis to ensure that a complete treatment is performed while respecting anatomical integrity and reducing the risk of iatrogenic fertility impairment. Moreover, in treating DIE, a multidisciplinary approach is mandatory, which must include general surgeons and urologists, to offer to the patients at the time of the procedure, the best specific skills coming from different specialists in treating DIE (12, 13). Although DIE is a very challenging surgical please introduce it is an expression of benign condition that affects women in their fertile age, and the most aggressive surgical solution and related complication are not always acceptable for the patient. Moreover, knowledge of the pathogenic process behind endometriosis and its symptoms is nowadays clear (14). All of the genetic, immunological and overall endocrinological involvements have been stressed by several authors, achieving a DOI: 10.5301/je.5000206

Abstract 1653: Complement roles in endometriosis and endometriosis-associated ovarian cancer

Abstract Introduction: Endometriosis is a largely benign, chronic inflammatory disease defined by the presence of endometrial-like glands surrounded by stroma. Epidemiologic studies suggest that endometriosis is an independent risk factor for endometrioid and clear cell epithelial ovarian tumors, collectively called endometriosis-associated ovarian cancers (EAOC). Histopathology findings demonstrate that EAOC occur in the presence of atypical endometriosis (AE), often found in direct continuity with the tumor, suggesting AE as the transitioning entity from benign lesions to malignant variants. Although it is widely accepted that chronic inflammation drives cancer, immune deregulation in chronic precursor lesions to ovarian cancer have not been studied in a systematic way. Experimental procedure: We extracted RNA from 135 paraffin tissue blocks comprising of normal endometrium (n=32), benign endometriosis consisting of ovarian and extra ovarian endometriosis cases (n=30,) atypical endometriosis (n=15) and EAOC, (n=43). Serous tumors (n=15) were included as non-endometriosis associated controls. Using Nanostring and the nCounter® GX Human Immunology Kit, we profiled a total of 511 immune genes. Cluster analyses and differential expressions (DE) were calculated using EdgeR. Protein expression of candidate proteins was validated with immunohistochemistry (IHC). To identify mechanisms of complement activation during early stages of genomic instability, we used murine cell lines derived from mice with conditional mutations in Kras and Pten pathways. Results: Nanostring immune gene expression profile eveal the predominant role of adaptive immunity and of the adaptive-innate immune cross-talk. The complement pathway was most prominently expressed, suggesting its roles as one of the major immune pathways involved in the transition from chronic endometriosis to atypical (premalignant) endometriosis and to EAOC. Complement pathway genes were upregulated in human endometriosis and atypical endometriosis. Tissue deposition of several complement components and changes in peripheral blood were confirmed by IHC and ELISA, respectively. Genomic instability in murine ovarian cancer cell lines with conditional mutations resulted in upregulation of complement genes expression in epithelial cells, but without an advantage on cell death. These findings further support a paradigm shift on complement roles in cancer, suggesting its pro-tumorigenic roles. Conclusions: We performed the first comprehensive gene profile of the tissue immune microenvironment in benign endometriosis, EAOC and precursor lesions and identified the previously unrecognized roles for the complement pathway. Complement activation may be an early trigger of inflammation and an early link between epithelium and immune environment. These findings have high translational potential for immune therapy and prevention in EAOC. Citation Format: Swati Maruti Suryawanshi, Xin Huang, Raluca Budiu, SungHwan Kim, George Tseng, Esther Elishaev, Marcia Klein-Patel, Ted Lee, Suketu Mansuria, Robert Edwards, Anda Vlad. Complement roles in endometriosis and endometriosis-associated ovarian cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1653. doi:10.1158/1538-7445.AM2014-1653

Endometriosis de localización extraovárica. Nuestra casuística en 10 años

IntroductionEndometriosis is a gynecological disease with a prevalence of about 5% to 10% of women. Localization is usually pelvic but in a small group of patients the disease can be localized elsewhere. Material and methodsWe performed a descriptive, observational and retrospective study of the medical records of 26 patients treated surgically for extraovarian endometriosis at the University General Hospital of Ciudad Real between January 2003 and January 2013. ResultsOur series included 26 patients who underwent surgery for extraovarian endometriosis. In order of frequency, the locations were the abdominal wall, umbilicus, vulva, appendix, ileum, hernia sac and colon. DiscussionThe frequency of extrapelvic endometriosis is very low. The treatment of choice is surgery. Resection with adequate margins reduces the chances of recurrence.

Magnetic resonance imaging as a non-invasive detection tool for extraovarian endometriosis – own experience

Endometriosis--due to its high incidence, associated pain and infertility--constitutes an important problem in gynecological practice. The Polish Gynecological Society Expert Panel recommends to perform magnetic resonance imaging (MRI) prior to laparoscopy The purpose of this study is to present the usefulness of MRI in the diagnosis of extraovarian endometriosis on the basis of own experience. The material consisted of 35 patients, aged 15-52 (mean 36.5 years), who were diagnosed with extraovarian endometriosis on MRI. MR examinations were performed with 1.5 T scanners according to a routine protocol, which incorporates the LAVA sequence of dynamic contrast studies protocol because of thin sections. Extraovarian endometriosis was isolated in 24 patients (68.6%), while in 11 (31.4%) it coexisted with ovarian endometriomas. In 23 cases (65.7%) extraovarian endometriosis was found in one place, in 12 (34.3%)--in two or more locations. Endometriosis was found in the following locations: abdominal wall--11 cases (37.4%), uterine body--9 (25.7%), posterior vaginal fornix--7 (20%), wall of the rectum and sigmoid colon--5 (14.3%), pararectal space--5, uterine cervix--4 (11.4%), Douglas pouch--3 (8.6%), Fallopian tube--2 (5.7%), wall of the small intestine--1 (2.8%), and urinary bladder--1. Adhesions were observed in 28.6% of the patients. MRI is an important addition to the non-invasive diagnosis of extraovarian endometriosis and should be performed before treatment, especially surgical one. The inclusion of fat saturated T1 sequence from the dynamic contrast examination in the study protocol increases the likelihood of detecting small endometrial implants.